Enzymes and prereceptor signal modification

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Tissue metabolism of ligand is now established as an important prereceptor signaling pathway in endocrinology. 11β-Hydroxysteroid dehydrogenase activity, by inactivating cortisol and corticosterone, regulates ligand access to the glucocorticoid receptor and in the kidney and distal colon enables the much lower circulating concentrations of aldosterone to occupy the mineralocorticoids receptor. Two distinct 5α-reductase and 5 deiodinase enzymes, respectively, convert testosterone and rhyroxine to the potent ligands dihydrotestosterone and triiodothyronine iodothronine. Other enzymes, such as aromatase, and 3β- and 17β-hydroxysteroid dehydrogenase, also play a key role in mediating peripheral sex hormone action. Finally, an uncharacterized isomerase, by catalyzing the conversion of ail-trans retinoic acid to 9-cis retinoic acid, dictates specificity of retinoid action. This review focuses on the recent clinical and scientific advances in this area. The role of these enzymes in normal physiology is apparent, and alterations in their activities can have profound consequences Factors that control the tissue expression and activity of these enzymes are emerging and will be a major impetus of research in the future.

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